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More evidence supports the association of PPP3CC with schizophrenia

Molecular Psychiatry volume 12, pages 966–974 (2007)Cite this article

Abstract

Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the γ isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P=0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P=0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266–rs2272080) and seven-SNP haplotype (rs2461491–rs2469758–rs2461489–rs2469770–rs2449340–rs1482337–rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P<0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P<0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia.

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Acknowledgements

We gratefully acknowledge the SNP genotyping work performed by the National Genotyping Center (NGC), National Science Council, Taiwan and the assistance provided by the Microarray and SNP Core Facility for Genomic Medicine in NTUH. This study was supported by Grants from the NRPGM, National Science Council, Taiwan (NSC91-2314-B-002-216, NSC91-3112-B-002-011, NSC92-3112-B-002-019, NSC93-3112-B-002-012, NSC94-3112-B-002-020, NSC95-3112-B002-011), the National Health Research Institute, Taiwan (NHRI-EX-91,92,93,94-9113PP; NHRI-EX-9511PP) and the National Institute of Health, USA (IR01 MH 59624-01).

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Authors and Affiliations

  1. Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Taipei, Taiwan

    Y L Liu

  2. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    C S J Fann, C C Chang, W C Yang & Y S Jou

  3. Department of Psychiatry, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan

    C M Liu, T J Hwang, M H Hsieh, C C Liu, W J Chen & H-G Hwu

  4. National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    S I Hung

  5. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    S I Hung

  6. Department of Medical Research, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    S L Yu

  7. Ju-Shan Mental Hospital, Taoyuan, Taiwan

    M M Tsuang

  8. National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    J Y Wu

  9. Department of Psychiatry and Neuroscience & Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, NY, USA

    S V Faraone

  10. Departments of Epidemiology and Psychiatry, Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard University, Boston, MA, USA

    M T Tsuang

  11. Institute of Behavioral Genomics, University of California, San Diego, CA, USA

    M T Tsuang

  12. Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan

    W J Chen & H-G Hwu

  13. Department of Psychology, College of Science, National Taiwan University, Taipei, Taiwan

    H-G Hwu

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Liu, Y., Fann, C., Liu, C. et al. More evidence supports the association of PPP3CC with schizophrenia. Mol Psychiatry 12, 966–974 (2007). https://doi.org/10.1038/sj.mp.4001977

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